Introduction

Ependymal cysts represent an infrequent type of benign congenital neuroglial cysts characterized by a fluid-filled cavity surrounded by ciliated epithelial (ependymal) cells lying directly on the brain parenchyma or on an astroglial layer.¹ In people, they frequently appear intraparenchymal and paraventricular inside the white matter of the temporoparietal and frontal lobes, but they also may be located in the subarachnoid space, brainstem, and cerebellum.¹ Their etiology and pathogenesis are not completely understood but are considered to originate from sequestration of developing neuroectoderm during embryogenesis or by migration of ependymal cells from the ventricular system.¹ In human literature, ependymal cysts exhibit a wide range of symptoms depending on their location.² Surgical resection is considered the treatment of choice in all symptomatic patients and also should be considered in asymptomatic patients.² However, there is no consensus regarding the surgical techniques including cystoventricular fenestration, cystosubarachnoid fenestration, cystosubarachnoid shunt, subtotal resection with and without marsupialization, and cystoperitoneal shunt.² Total resection has been suggested as the optimal treatment option but might not be possible depending on the size, location, and existing adherences.² Clinical improvement has been reported in 83% of the patients undergoing surgery with a reduction of the cyst size in those surgically treated patients with a mean follow-up of 44.3 mo with no recurrence.³

In veterinary medicine, ependymal cysts seem to be even rarer than in people and have only been reported in three dogs, as there may be others diagnosed but not reported, two of them only after postmortem examination.^4–6 In one case, partial excision was achieved via endoscopy-assisted transsphenoidal hypophysectomy, but 73 days later, clinical recurrence led to euthanasia.⁶

The goal of this case report is to describe the complete successful resection of an ependymal cyst in the fourth ventricle in a dog and its long-term outcome.

Case Report

A 6 yr old male entire American Staffordshire terrier weighing 36.2 kg was referred with a 4 mo history of incoordination, collapsing episodes with extensor rigidity, and positional left horizontal nystagmus. The general physical examination was unremarkable. The neurological examination showed bright and alert mentation, slight right head tilt, cerebellar ataxia, and postural reaction delays in the left thoracic and pelvic limbs. The combination of left central signs and right head tilt indicated a paradoxical vestibular syndrome, suggesting a lesion in the left central vestibular system and cerebellum. The differential diagnoses included infectious or immune-mediated meningoencephalitides, intracranial arachnoid diverticulum, intracranial cyst (dermoid, epidermoid, colloid, ependymal, epithelial, or choroid), cerebellar abiotrophy of the American Staffordshire terrier, or neoplasia (choroid plexus papilloma/carcinoma, meningioma). Hematology and complete biochemistry profile results were within reference ranges, and thoracic radiographs showed no abnormalities. This client-owned dog was not an experimental animal, and all consents for all procedures, including surgery, were signed by the owner after explaining all possible complications. All procedures followed international recognized best practice for the welfare of animals. A brain computed tomography (CT) scan^a with a slice width of 0.625 mm, a helical pitch of 1, an image production interval of 0.625 mm, 120 kV, and an automatic interval between 80 and 200 mAs was performed under general anesthesia. The anesthetic protocol consisted of direct induction with lidocaine^b (2 mg/kg IV) and propofol^c (5 mg/kg IV). The dog was positioned in sternal recumbency and iohexol^d (400 mg/kg) was used as IV contrast medium. A slightly right-sided, hypoattenuating, round, well-defined lesion with peripheral contrast enhancement was observed in the fourth ventricle, displacing the caudal cerebellum (Figures 1A, B). Enlargement of the ventricular system was observed rostral to the lesion. These findings were consistent with an intraventricular cyst and secondary obstructive hydrocephalus. A presumptive diagnosis of dermoid, epidermoid, ependymal, or choroid cyst and secondary obstructive hydrocephalus was established. Medical treatment with prednisone^e was started at 0.5 mg/kg per os (PO) q 12 hr with a tapering course for 2 wk.

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Despite an initial improvement, there was a deterioration of the neurological status 1 mo after the initial investigation. Although the same prednisone regimen was started again, the clinical response was minimal to nil, so surgical excision was advised. Two months after the CT scan, surgery was performed to remove the lesion. The anesthetic protocol consisted of methadone^f (0.2 mg/kg intramuscularly) as premedication and lidocaine (2 mg/kg IV), midazolam^g 0.5 mg/kg, and propofol (5 mg/kg IV) as induction before intubation with a reinforced endotracheal tube to avoid kinking. The dog was maintained with a propofol continuous rate infusion (CRI) (0.4 mg/kg/min), ketamine^h CRI (10 µg/kg/min), and lidocaine (20 mg/kg/min)/midazolam (0.2 mg/kg/min) CRI with a constant O₂ flow of 0.2 L/min. The body was placed in sternal recumbency with the neck flexed to achieve a 90º angulation of the occipito-atlanto-axial joint approximately in order to obtain the widest possible opening of the foramen magnum. During the procedure, maropitantⁱ (1 mg/kg IV), dexamethasone^j (0.1 mg/kg IV), pantoprazole^k (1 mg/kg IV), cefazoline^l (40 mg/kg IV), and methadone (0.2 mg/kg IV) were administered. Physiological and anesthetic parameters monitored included heart rate, respiratory rate, rectal temperature, invasive blood pressure measurements (systolic, mean, and diastolic blood pressure), end-tidal CO₂, O₂ saturation, tidal volume, airway pressure, and compliance. Ringer’s lactate^m was administered IV at 180 mL/hr for maintenance fluid therapy. The brachiocephalic; splenius; semispinalis capitis; rectus capitis dorsalis major, intermedius, and minor; and obliquus capitis caudalis muscles were separated from the midline and retracted laterally to expose the occipital bone, dorsal lamina of the atlas, and spinous process of the axis. A suboccipital craniectomy with pneumatic burrⁿ was performed to expose the caudal cerebellum and myelencephalon. A grayish cystic structure with smooth surface and fluctuating consistency was observed at the level of the obex between the cerebellum and the medulla oblongata. At this stage, mannitol^o IV at 0.25 g/kg in slow infusion was administered in an attempt to prevent reperfusion injury after cyst removal. The cystic content was aspirated using a sterile 1 mL syringe and 21 G needle. The content was dense and of brown color. Cholesterol crystals were found in the cytological examination (Figure 2A). Once drained, the cyst wall was carefully separated from the surrounding tissue until complete macroscopic resection was achieved using blunt dissection and bipolar electrocautery. The bony defect was covered with synthetic hemostatic collagen^p, but the soft tissue layers were sutured with monofilament 2/0 absorbable synthetic depoli-p-dioxanone suture^q for the musculature and subcutaneous layers and a monofilament 3/0 absorbable synthetic glycolonate suture^r for the skin in subcuticular continuous pattern. A pre- and postcontrast brain computed tomography scan was performed immediately after the surgery and no macroscopic cystic tissue was identified, although mild pneumocephalus was observed (Figures 1C, D).

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The entire cyst capsule was histopathologically studied by a board-certified pathologist and revealed a simple cubic to cylindrical epithelium with apical cilia surrounded by a loose fibrillar tissue consistent with an ependymal cyst (Figure 2B).

There was neurological deterioration immediately after surgery including severe vestibulo-cerebellar ataxia along with nonambulatory tetraparesis and severe spontaneous left horizontal nystagmus. During the hospitalization, the patient received cefazoline (20 mg/kg IV q 8 hr), maropitant (1 mg/kg IV q 24 hr), betahistine dihydrochloride^s (0.5 mg/kg PO q 8 hr; as antivertiginous), and dexamethasone (0.1 mg/kg IV q 24 hr). Twenty-four hours after surgery, the dog was able to walk with assistance, showing marked hypermetric gait, and was discharged 4 days after surgery with spontaneous nystagmus but able to walk with little assistance. Home treatment consisted of cefalexin^t (20 mg/kg PO q 12 hr) for 7 days, betahistine dihydrochloride (0.5mg/kg PO q 8 hr) for 14 days, and prednisone (0.5 mg/kg PO q 12 hr), the latter with a tapering course for 2 wk. In-person rechecks were carried out 1, 2, and 6 wk after surgery. At the time of the last examination, only slight cerebellar ataxia was observed. Subsequent rechecks were obtained via telephonic conversations with the owner and/or the referring veterinarian as well as video recordings. Four and a half years after the surgery, the dog remains stable with an excellent quality of life, having only short episodes of balance loss when turning abruptly. No signs of clinical relapse have been noticed.

Discussion

True intracranial cysts are closed epithelium-lined sacs or capsules within the cranial vault containing a liquid or semisolid substance. They may cause neurological signs directly by compressing brain parenchyma or indirectly by blocking cerebrospinal fluid (CSF) circulation and causing obstructive hydrocephalus.⁷ Several types of cysts have been described in dogs depending on the origin of the lining cells and their content. Epidermoid cysts are lined by stratified squamous epithelium that gradually grows as desquamated keratinocytes, keratinaceous debris, and cholesterol accumulates in the lumen.⁷ Dermoid cysts also contain epidermal adnexal structures such as hair follicles, sebaceous and apocrine glands, and fat.⁷ Choroid plexus cysts are surrounded by a choroid epithelial lining, and their content tends to be a clear CSF-like substance, but with a higher protein content.⁷ Finally, ependymal cysts are thin walled and filled with clear serous fluid secreted from ependymal cells (columnar cells, with or without cilia).¹ Conflicting information exists in human literature on the nature of ependymal cysts. Whereas some authors include such cysts in the broader category of neuroepithelial cysts, for other authors, they should be classified as a different entity based on immunohistochemistry with positive glial fibrillary acidic protein.⁸

In general, all cysts tend to show a hypointense signal in T1-weighted images and hyperintense in T2-weighted images with MRI studies (except for dermoid cysts, which show hyperintense signal in both T1-weighted and T2-weighted images owing to their fat content), with incomplete suppression during fluid attenuation inversion recovery sequences, and variable degrees of contrast enhancement.^1,7 During CT imaging, they usually appear as well-defined, circular, hypoattenuating lesions showing mild peripheral enhancement, similar to our clinical case. In addition, they are most frequently located in the caudal fossa.^1,7 Because most cysts have similar characteristics on MRI and CT, histopathological analysis is necessary for their definitive diagnosis.

Ependymal cysts have only been described in three dogs previously, two in the caudal fossa^4,5 and one in the middle cranial fossa.⁶ The definitive histopathological diagnosis was obtained following postmortem examination in all cases,^4–6 although a neuroendocrine or ependymal origin was suspected after cytology in one case.⁶ Both previous cases of caudal fossa cysts^4,5 showed similar presentation and radiological findings to our case report, with ataxia, head tilt, and postural reaction delays at the time of presentation and a well-marginated, round and ring-enhancing mass during MRI studies. One case was an 11 wk old male Staffordshire bull terrier euthanatized at the time of diagnosis,⁴ whereas the second was a 4 yr old intact female Shetland sheepdog with severe neutrophilic pleocytosis in the CSF at the time of diagnosis and was treated with prednisone, ciprofloxacin, clindamycin, and fluconazole, showing a marked improvement. Sixteen months after treatment was initiated, the dog suffered a clinical relapse and prednisone was reintroduced. However, 32 mo after the initial treatment, the dog was found in lateral recumbency and was euthanatized.⁵ The only surgically treated case was a 9 yr old spayed female mixed-breed dog showing intermittent head tremors, obtundation, long-standing blindness, and a tendency to seek confined places. The cyst was located in the suprasellar region and extended toward the frontal area, compressing the optic chiasm and hypothalamic region. An endoscopy-assisted transsphenoidal hypophysectomy was performed to remove the pituitary gland, drain the cyst, and partially excise the cyst wall. Seventy-three days after surgery, cyst recurrence was apparent on MRI and the dog was euthanatized at the owners’ request.⁶ Because of the small number of reported cases, including ours, it is not possible to draw conclusions on the best treatment for dogs.

Although surgical resection is considered the treatment of choice in all symptomatic human patients,² nearly half of the reported veterinary cases with histopathologically confirmed caudal fossa intracranial cysts were medically treated^5,9 or euthanatized at the time of diagnosis.^4,7,10 Animals treated conservatively received prednisone and survived for 4 mo⁹ and 3 yr⁵ until their neurological status worsened and they were humanely euthanatized. Seven dogs underwent surgical excision,^11–17 but only five survived the surgery. In three dogs, incomplete removal resulted in relapse or death within 4,¹³ 6,¹⁷ and 36 wk¹⁴ after surgery, with four dogs lost to follow-up 5–18 mo after surgery.^11,12 In human medicine, complete resection has been suggested as the best treatment option; however, there is no general consensus.² The most appropriate treatment option should be chosen based on size and location on a case-by-case basis. Complete excision is not always possible, and other techniques have been described to drain the accumulated fluid, including cystoventricular fenestration, cystosubarachnoid fenestration, cystosubarachnoid shunt, subtotal resection with and without marsupialization, and cystoperitoneal shunting.² Most surgically treated veterinary cases have attempted to achieve complete removal through a suboccipital craniectomy,^11,14–17 the same approach used in human medicine for ependymal cysts located in the fourth ventricle.¹⁸ In one dog, a left rostrotentorial craniectomy was elected owing to the telencephalic location of the cyst,¹² and in another dog, a ventriculoperitoneal shunt was placed to alleviate secondary hydrocephalus due to CSF obstruction.¹³

The scarce information available in the veterinary literature precludes any conclusion regarding the best treatment option in dogs with caudal fossa cysts. However, based on human recommendations, when possible, complete surgical removal should be considered.²

To the authors’ knowledge, this is the first reported case of an intraventricular ependymal cyst in the caudal fossa completely removed in a dog with long-term survival and follow-up.

Conclusion

Ependymal cyst should be included in the list of differential diagnoses of any cystic mass in the fourth ventricle in dogs. Despite initial postsurgical neurological deterioration, clinical signs in our patient improved and complete excision appears to have been successful and curative.

The authors wish to thank all clinicians and support personnel of the hospital for their help and commitment to manage this challenging case. Publication funding was supported by IVC Evidensia GVMB Research Fund.